The objectives of this proposal are: 1) to test the hypothesis that survival of kidney and bone marrow grafts in humans is related to the response of recipients to hepatitis B infection before transplantation; 2) to gain insight into the mechanism by which responses to hepatitis B virus might be related to responses to organ grafts. Specifically, to test the hypothesis that there is cross reactivity between antigenic determinants on HEV and a male-associated antigen. Studies of first kidney transplants in 197 recipients showed that grafts from male donors in anti-HBs(plus) female recipients have significantly poorer survival than grafts from male donors in anti-HBs(minus) recipients. Other factors which contribute to graft rejection in this population are relatedness and HLA matching of donor and recipient, pre-transplantation blood transfusion and pre-transplantation nephrectomy. These factors are being included in a multivariate analysis of risk of graft rejection. A multifactorial model will be developed which we will then test in another population of transplant recipients. Immunohistological studies of rejected kidney grafts to assess the role of anti-HBs in graft rejection are in progress. Thus far, no association has been found in humans between anti-HBs and antisperm antibodies.